First-in-human Study of BAY2287411 Injection, a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Tumors Known to Express Mesothelin

Bayer

Status and phase: Completed; Phase 1

Conditions: Advanced Pancreatic Ductal Adenocarcinoma (Optional, Dose Expansion, Not Initiated); Advanced Recurrent Serous Ovarian Cancer; Advanced Recurrent Malignant Pleural Epithelioid Mesothelioma; Advanced Recurrent Malignant Peritoneal Epithelioid Mesothelioma

Treatments: Drug: BAY2287411

Study type: Interventional

Funder types: Industry

Identifiers

NCT03507452

18795

2017-004052-29 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to evaluate, in patients with tumors known to express the protein mesothelin, the following properties of BAY2287411 injection:

• safety (to identify, assess, minimize, and appropriately manage the risks associated to the study drug)
• tolerability (the degree to which side effects can be tolerated by your body)
• maximum tolerated dose
• pharmacokinetics (the effect of your body on the study drug)
• anti-tumor activity
• recommended dose for further clinical development

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent
• Male or female subjects ≥ 18 years of age
• ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1
• Patients with advanced malignant epithelioid mesothelioma or advanced recurrent serous ovarian cancer, who have exhausted available therapeutic options; in addition, in the dose expansion part of the study, patients with metastatic pancreatic adenocarcinoma, who have exhausted available therapeutic options
• Availability of fresh or archival tumor tissue samples
• Adequate bone marrow, liver and renal function, as assessed by pre-defined laboratory requirements (within 28 days before start of study drug treatment)
• A negative serum pregnancy test in women of childbearing potential (WOCBP) performed within 7 days before the start of study drug administration. Women and men of reproductive potential must agree to use highly effective methods of contraception, when sexually active.

Exclusion criteria

• Impaired cardiac function, clinically significant cardiac disease or cardiac arrhythmias
• Pericarditis (any CTCAE grade) or pericardial effusion (CTCAE Grade ≥ 2)
• Left Ventricular Ejection Fraction (LVEF) < 50% (as measured at screening by echocardiogram).
• History of anaphylactic reactions to monoclonal antibody therapy
• History of Myelodysplastic syndrome (MDS)/treatment-related acute myeloid leukemia (t-AML) or with features suggestive of MDS/AML
• Infections of CTCAE (Common Terminology Criteria for Adverse Events) version 5.0 Grade 2 not responding to therapy or active clinically serious infections of CTCAE Grade >2; known human immunodeficiency virus (HIV) infection; active hepatitis B virus (HBV) or hepatitis C virus (HCV)infection requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator's discretion provided that the disease is stable and sufficiently controlled under treatment
• Known brain, spinal or meningeal metastases

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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36 participants in 7 patient groups

Dose escalation cohort a

Experimental group

Description:

Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 mg.

Treatment:

Drug: BAY2287411

Drug: BAY2287411

Dose escalation cohort b

Experimental group

Description:

Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with a total antibody dose within the range of 10 - 50 mg.

Treatment:

Drug: BAY2287411

Drug: BAY2287411

Dose Expansion Cohort 1

Experimental group

Description:

Subjects with advanced recurrent epithelioid mesothelioma or serous ovarian cancer, who have exhausted available therapeutic options Dose / Regimen 1 (to be determined after completion of the dose escalation)

Treatment:

Drug: BAY2287411

Drug: BAY2287411

Dose Expansion Cohort 2

Experimental group

Description:

Subjects with advanced recurrent epithelioid mesothelioma or serous ovarian cancer, who have exhausted available therapeutic options Dose / Regimen 2 (to be determined after completion of the dose escalation)

Treatment:

Drug: BAY2287411

Drug: BAY2287411

Dose expansion Cohort 3 (optional)

Experimental group

Description:

Subjects with histologically or cytologically confirmed unresectable, metastatic or locally advanced pancreatic ductal adenocarcinoma Dose / Regimen to be determined

Treatment:

Drug: BAY2287411

Drug: BAY2287411

Dose escalation cohort c

Experimental group

Description:

Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 - 150 mg mg.

Treatment:

Drug: BAY2287411

Drug: BAY2287411

Dose escalation cohort d

Experimental group

Description:

Subjects with either advanced recurrent epithelioid mesothelioma or serous ovarian cancer who have exhausted available therapeutic options. The dose of Thorium-227 will start at 1.5 MBq and increase in steps of 1.0 or 1.5 MBq, with antibody doses of 10 - 400 mg.

Treatment:

Drug: BAY2287411

Drug: BAY2287411